Slow Viruses

World of Microbiology and Immunology
COPYRIGHT 2003 The Gale Group Inc.

Slow viruses

Historically, the term "slow virus infections" was coined for a poorly defined group of seemingly viral diseases which were later found to be caused by several quite different conventional viruses , also unconventional infectious agents. They nevertheless shared the properties of causing diseases with long incubation periods and a protracted course of illness, affecting largely the central nervous and/or the lymph system and usually culminating in death. The slow virus concept was first introduced by the Icelandic physician Bjorn Sigurdsson (1913–1959) in 1954. He and his co-workers had made pioneering studies on slow diseases in sheep including maedivisna and scrapie. Maedi is a slowly progressive interstitial pneumonia of adult sheep while visna is a slow, progressive encephalomyelitis and the same virus, belonging, to the lentivirus subgroup of retroviruses , was found to be responsible for both conditions.

Since the original isolation of the maedi-visna virus, concern with slow viral infections, both in animals and in humans, has grown. Research on sheep lentiviruses and their pathogenesis has continued to this day and received an important impetus in the 1980s with the recognition of the devastating condition in humans known as acquired immunodeficiency syndrome (AIDS ). AIDS shared many of the attributes of slow virus infections in animals and led virologists to suspect, then to identify, the lentivirus causing AIDS: the human immunodeficiency virus or HIV . Questions posed by Bjorn Sigurdsson's work on maedi-visna also became the central pathogenic questions of HIV disease. For example: how and where does HIV persist despite an initially robust and long-sustained immune response? How does HIV actually destroy the tissues it infects? Why do these events unfold so slowly? Final answers to all these questions have still not been found and there is much research still to be done on the lentiviruses but Sigurdsson's contribution to HIV research through the study of maedi-visna is now recognized.

Other slow virus infections of humans due by conventional viruses include progressive multifocal leukoencephalopathy (PML) caused by the JC papovavirus. This is an opportunistic infection in hosts that have defective cell-mediated immunity and the majority of human cases now occur in HIV 1 infected individuals. Patients present with progressive multifocal signs including visual loss, aphasia (difficulty speaking), seizures, dementia, personality changes, gait problems, and less commonly, cerebellar, brain stem, and spinal cord features. Death occurs within weeks to months of clinical onset. Subacute sclerosing panencephalitis (SSPE), another slow infection, has been identified as a rare consequence of chronic persistant infection by the measles (rubella) virus, causing an insidious syndrome of behavioral changes in young children. Patients develop motor abnormalities, in particular myoclonic jerks, and ultimately become mute, quadriplegic, and in rigid stupor. SSPE is found worldwide with a frequency of one case per million per year. Progressive rubella panencephalitis is another very rare slow virus infection of children and young people caused by the same virus. Most patients have a history of congenital or acquired rubella and the clinical course is more protracted than in SSPE with progressive neurologic deficit occurring over several years. A third slow virus of humans that has had some publicity in recent years is the human T-cell leukemia virus (HTLV ) types 1 and 2 which are associated with adult T-cell leukemia. It was initially thought that the causative agent of AIDS was related to HTLV though it later became clear that whereas HTLV 1 and 2 are both oncogenic ("cancer producing") retroviruses, HIV belongs to the lentivirus sub-group.

An unconventional agent causing slow infections has now been identified as a non-viral "proteinaceous, infectious" agent, or prion. Prions give rise to the group of diseases now called transmissible spongiform encephalopathies. In animals these include scrapie in sheep and bovine spongiform encephalopathy (BSE) in cows. Human prion infections include rare dementing diseases like kuru, Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker (GSS) syndrome, and fatal familial insomnia (FFI). The prion agent is replicated without provoking any antibody response, appears not to have any recognizable nucleic acid component, and is resistant to conventional inactivation techniques for infectious agents. Current evidence suggests that the prion protein is an abnormal isoform of a normal host encoded protein known as PrP, which is coded on the short arm of chromosome 20. Prions appear to "replicate" by a novel form of protein-protein information transfer, the abnormal PrP seemingly inducing the normal protein to undergo a structural change into the abnormal form. Most pathological changes observed with transmissible spongiform encephalopathies are confined to the brain; however, scrapie-induced disorders of the pancreas have also been described. The neuropathology sometimes shows a dramatic spongiform disruption of brain tissue but may also be subtle and non-characteristic, even at the terminal stages of the disease. In the latter cases, diagnosis has to rely on features like clinical signs, transmissibility, detection of abnormal PrP or identification of mutations in the PrP gene .

In humans, prion diseases may be sporadic, acquired or inherited. Iatrogenic transmissions of the prion have occurred following medical procedures such as pituitary growth hormone injections, where the hormone source was contaminated with prion tissue, or corneal transplants, where a patient accidentally received an infected cornea. The first recognized human prion disease was kuru, which emerged among the South Fore people of New Guinea and is now generally thought to have been transmitted by the practice of ritual cannibalism. CJD is today the most common human prion disease occurring worldwide with a frequency of about one per million per year. The peak incidence occurs in older people between the ages 55 and 65 although recently a "new variant" has emerged in the U.K., which affects individuals at a much earlier age. It is widely believed that the new variant CJD is closely related to the variety causing BSE in cattle and may be contracted by the ingestion of infected beef.

Inherited prion disease can arise from specific point mutations in the PrP gene. Perhaps 10–15% of CJD cases are familial with an autosomal dominant pattern of inheritance. Gerstmann-Straussler-Scheinker syndrome is another rare familial condition that is vertically transmitted in an apparently autosomal dominant way. As with other prion diseases it can be horizontally transmitted to non-human primates and rodents through intracerebral inoculation of brain homogenates from patients with the disease. The exact incidence of the syndrome is unknown but is estimated to be between one and ten per hundred million per year and the condition appears to be an allelic variant of familial Creutzfeldt-Jakob disease. Fatal familial insomnia is the third most common inherited human prion disease. The region of the brain most affected in this condition is the thalamus which monitors sleep patterns. The symptoms of the disease are characterized by progressive insomnia and, as with other prion diseases, eventual motor signs.

See also Viral genetics

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slow virus

The Columbia Encyclopedia, 6th ed.

Copyright The Columbia University Press

slow virus, technically a virus, such as a lentivirus, that causes symptoms in an infected host long after the original infection and progresses slowly. Although many viruses fit this description, the term slow virus is usually reserved for the first recognized lentiviruses, such as the virus that causes visna (a disease of sheep). A slow virus was proposed as a cause for those diseases now generally recognized as prion diseases (e.g., Creutzfeld-Jacob disease and scrapie).

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slow virus

slow virus Any of a group of quasi-viral or subviral agents formerly thought to be responsible for the diseases scrapie in sheep and bovine spongiform encephalopathy (BSE) in cattle. These diseases are now generally regarded as being caused by abnormal prion proteins.

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